Flaviviridae are arboviruses (arthropod-borne virus) mainly transported by mosquitoes and blood-sucking ticks. They are small encapsidated viruses and their genomes consist of infectious single-stranded and linear RNA of positive polarity. In Man, flaviviruses cause deadly hemorrhagic fever or meningoencephalitis. Yellow fever, dengue fever and Japanese encephalitis are the main tropical flaviviroses. Other important human flaviviroses are Saint Louis encephalitis, tick-born European encephalitis and West Nile fever.
West Nile fever is a zoonosis associated with a flavivirus which was first isolated in Uganda in 1937. Its transmission cycle calls for birds as the main reservoir and for blood sucking mosquitoes of the Culex genus as vectors. Migratory viremic birds transport the virus to far-away regions where they transmit it anew to ornithophile mosquitoes of the Culex genus. Many species of mammals are permissive for the West Nile virus. Horses are particularly sensitive to the disease but do not participate in the cycle of transmission. West Nile fever is endemic in Africa, Asia, Europe and Australia. Phylogenic studies have revealed the existence of two strains of viruses: viral line 1 has a worldwide distribution, and viral line 2 is essentially African. Viral line 1 was responsible for enzooties in Romania (1996), Russia (1999), Israel (1998-2000) and more recently in North America where the virus had never been detected before 1999. The viral strains isolated during the recent epidemics in Israel and the United-States are more than 99.7% identical. In the Middle-East and North America, where the virus has taken root, an important bird mortality rate has been observed among infected birds, notably in Corvidae. In North America, over 4000 subjects were infected with the West Nile virus, 250 of which died between the months of August and December 2002. At the present time, zoonosis is observed in all regions of the United States. At the moment, there exists no human vaccine or specific therapy against West Nile fever.
In temperate and sub-tropical regions, human infections may occur during the fall season. When a subject is bitten by an infected mosquito, the incubation period lasts approximately one week but less than 20% of people infected with the West Nile virus ever go on to clinical manifestations. In its benignant form, the viral infection manifests itself by an undifferentiated febrile state associated with muscular weakness, headaches and abdominal pain. In less than 1% of infected subjects, encephalitis or acute aseptic meningitis may occur. Splenomegaly, hepatitis, pancreatitis and myocarditis are also observed. Flask paralyses similar to a poliomyelitic syndrome have recently been reported, but fatal cases of viral encephalitis (5% of patients having severe neurological disorders) mainly concern fragile subjects and the aged. Inter-human transmission of the virus has also recently been observed in the United-States in subjects having undergone organ transplants or having been perfused with contaminated blood products. Intra-uterine transmission of the virus has been reported in the United-States. The development of a human vaccine against the West Nile fever is a priority in view of the fact that the zoonosis has taken root in North America and is expected to propagate in the coming months to Central America, South America and the Caribbean where dengue fever and yellow fever are already rampant.
Therefore, there is a need for West-Nile virus (WNV) and/or Dengue virus derived peptides, and more particularly to polypeptides or polynucleotides derived from WNV and/or Dengue virus polypeptides or polynucleotides and their use in the preparation of compositions and vaccines.
The present invention fulfils these needs and also other needs which will be apparent to those skilled in the art upon reading the following specification.